SMOC™ Mouse Models For COVID-19 and Other Infectious Diseases

Mouse Models For COVID-19

ACE2-HU●● The● tropism●of● coronaviruses● is● determined●primarily●by●the●interaction●of●the●spike●(S)●protein●and●the●cellular●receptors●for●the●virus.

●● Human●angiotensin-converting●enzyme●2●(hACE2)●has●been●identified●as●a●major●receptor●for●SARS-CoV-2.●The●spike●protein●of●SARS-CoV-2●has●a●much●higher●binding●affinity● to●hACE2●than●do●those●of●mice,● rats,●and●other●animal●species,●which●correlates●with● the●much● lower● level●of●permissiveness●of●these●animals●to●this●virus.

●● These●transgenic●mice●express●hACE2●under●the●regulation●of●the●CAG●or●SPC●promoter.●An●internal●ribosome●entry●sequence●(IRES)●followed●by●the●reporter●gene●inserted●downstream●of●hACE2.

Figure 1. Luciferase●expression●of●the●CAG-hACE2-IRES-Luciferase●transgenic●mice

Coronavirus●disease●2019●(COVID-19)●is●an●infectious●disease●caused●by●severe●acute●respiratory●syndrome●coronavirus●2●(SARS-CoV-2).●SMOC●is●proud●to●offer●COVID-19●disease●models●aimed●at●understanding●the●pathogenesis●of●COVID-19●and●evaluating●the●efficacy●of●antiviral●drugs●and●vaccines.

Strain Name Tgtn(CAG-hACE2-IRES-Luciferase)

Cat. NO. NM-TG-200002

Background C57BL/6

Mutation Type Transgene

Strain Name Tgtn(SPC-hACE2-IRES-Luciferase)

Cat. NO. NM-TG-200003

Background C57BL/6

Mutation Type Transgene

Strain Name R26-(CAG-LSL-hACE2-IRES-tdTomato)

Cat. NO. NM-KI-200188

Background C57BL/6

Mutation Type Knock-in

Strain Name R26-(CAG-hACE2-IRES-EGFP)

Cat. NO. NM-KI-200189

Background C57BL/6

Mutation Type Knock-in

Phenotype

WT hACE2

换图

64000

25000

www.modelorg.com 2 SMOC Mouse Models For Covid-19 And Other Infectious Diseases

CD147-HU●● SARS-CoV-2● invaded●host●cells●via●a●novel●route●of●CD147-spike●protein● (SP).● SP●bound● to●CD147,● a●receptor●on●the●host●cells,●thereby●mediating●the●viral●invasion.

●● The●humanized●CD147● (hCD147)●mouse●strain●has●been●developed●by●inserting,●within●the●mouse●Cd147●locus,●a●chimeric●CD147●with●a●human●extracellular●domain,●a●murine● transmembrane●domain●and●a●murine●intracellular●domain.

Ace2-KO●● Acute● respiratory● distress● syndrome● (ARDS)● is●regarded●as●the●most●severe●form●of●acute●lung●injury●and●present●in●a●large●percentage●of●COVID-19●deaths.

●● ACE2●protects●mice● from●severe●acute● lung● injury/ARDS.

●● Ace2● knockout●mice●may●be● used● in● ARDS● and●COVID-19●research.

Figure 2. Expression●of●CD147● in● the● red●blood●cells●of●humanized●CD147●mice●is●detected●by●FACS.

Strain Name CD147-HU

Cat. NO. NM-HU-2000021

Background C57BL/6

Mutation Type Humanization

Strain Name Ace2-KO

Cat. NO. NM-KO-190906

Background C57BL/6

Mutation Type Knockout

WT hCD147

Q1-UL(0.01%)

Q1-LL(0.21%) Q1-LR(99.78%)

Q1-UR(0.02%)

102

102

103

103 104 105 106

104

105

106

Q1-UL(0.00%)

Q1-LL(0.01%) Q1-LR(0.69%)

Q1-UR(99.31%)

102

102

103

103 104 105 106

104

105

106

hCD

147

mTER119

SMOC Mouse Models For Covid-19 And Other Infectious Diseases 3 www.modelorg.com

Figure 3. Immune●profile●of●M-NSG●mice● ●humanized●with●human●HSCs.●

Figure 5. Kinetics●of●engraftment●of●PBMCs● from●different●donors●in●M-NSG●mice.●

Figure 6. Body●weights●of●PBMC●humanized●mice.Figure 4. HSC●humanized●mouse●support●development●of●both●Myeloid●and●Lymphoid●Cells

Humanized● immune●system●mice●may●be●useful● for●studies● into●human●immune●system●response●to●SARS-CoV-2●infection●and/or●vaccine●response.

Humanized Immune System Mice

Strain Name huPBMC-(M-NSG)

Cat. NO. NM-NSG-015

Strain Name huHSC-(M-NSG)

Cat. NO. NM-NSG-017

100

75

50

25

0

Weeks post HSC engraftment4wk 8wk 18wk 20wk

HSC humanized model

huC

D45

(%)

00 10 20 30 40

20

40

60

80

100

120

Days post inoculation

Donor 1Donor 2Donor 3Donor 4Donor 5Donor 6

PBMC chimeric rate

hCD

45 c

him

eric

rate

(%)

15

20

25

Body Weight

0 10 20 30 40Days post inoculation

Bod

y W

eigh

t (g)

Donor 1Donor 2Donor 3

Donor 4Donor 5Donor 6

CD3+CD8+

CD3+CD4+

CD56+C

D16+

CD14+C

D11b+

CD19+

Imm

une

cells

(%

)

0

20

40

60

% of Human CD45+ Cells in Peripheral Blood

www.modelorg.com 4 SMOC Mouse Models For Covid-19 And Other Infectious Diseases

Mouse Models For Hepatitis B

HBV-TG●● To●better●understand●the●roles●played●by●HBV●protein●expression,● full-length●HBV●genome●(adr●subtype,●C●genotype)● isolated●from●a●chronic●HBV●carrier●was●used●to●establish●the●HBV●transgenic●mice.

●● These●HBV-TG●mice●expressed●HBsAg●in●serum,●and●HBsAg●and●HBcAg● in● liver●and●kidney,●but●without●virus●replication1.

Alb-hNTCP●● NTCP,●also●known●as●SLC10A1●(solute●carrier● family●10●member●1),●acts●as● the● functional● receptor● for●hepatitis●delta●virus●(HDV)●and●hepatitis●B●virus●(HBV)2.

●● Expressing●human●NTCP●in●human●hepatoma●HepG2●cells●(HepG2-NTCP)●renders●these●cells●susceptible●for●HBV●infection3.

●● It● is●also●reported●that●mice●carrying●the●hNTCP/BAC●transgene●are●susceptible●to●infection●with●hepatitis●delta●virus●(HDV)●and●may●be●used●as●a●humanized●mouse●model●for●hepatitis●delta●virus●infection4.

●● The●H11-(Alb-NTCP-C9●tag-IRES-EGFP)●mouse●strain●of●SMOC●has●the●mouse●albumin●promoter●sequences●directing●expression●of●hNTCP●gene,●which●would●be●used●as●a●good●in●vivo●model● for●HBV●and●HDV●infection●research.

Hepatitis●B●is●an●infection●caused●by●the●hepatitis●B●virus●(HBV)●and●affects●an●estimate●of●240●million●people●worldwide●despite●the●availability●of●a●preventive●vaccine.●Medication●to●repress●viral●replication●is●available●but●a●cure●is●rarely●achieved.●The●lack●of●reliable●in●vivo●models●susceptible●to●HBV●infection,●has●limited●research●progress●in●the●past.●SMOC●is●proud●to●offer●HBV●research●mouse●models●aimed●at●studying●viral●pathogenesis●and●testing●novel●HBV●therapeutics.

Strain Name Tg(HBV)

Cat. NO. NM-TG-00003

Background B6.Cg

Mutation Type Transgene

Strain Name H11-(Alb-NTCP-C9●tag-IRES-EGFP)

Cat. NO. NM-KI-200054

Background C57BL/6

Mutation Type Knock-in

SMOC Mouse Models For Covid-19 And Other Infectious Diseases 5 www.modelorg.com

DPP4-HUModels for MERS-CoV infection

●● Middle●East●respiratory●syndrome-related●coronavirus●(MERS-CoV)●is●a●species●of●coronavirus●which●infects●humans,●bats,●and●camels.

●● Dipeptidyl●peptidase●4●(DPP4,●CD26)● is●the●receptor●for●the●MERS-CoV.

●● The● humanized●DPP4● (hDPP4)●mouse● strain● is●potentially●the●ideal●first●line●animal●model●for●efficacy●testing●of●therapeutic.

Mouse Models For Other Infectious Diseases

CD81&OCLN-HUModels for HCV infection

●● CD81●and●the●tight●junction●protein●claudin-1●(CLDN1)●naturally●form●a●complex●that●is●essential●to●HCV●entry●and●which●is●likely●regulated●by●the●Epidermal●Growth●Factor-Receptor●(EGFR)●and●the●GTPase●HRas.

●● The●hCD81●/hOCLN●double●knock-in●mouse●strain●may●be●more●susceptible●to●Hepatitis●C●Virus.

●● The●hCD81/hOCLN●mouse●strain●is●the●ideal●model●for●the●study●of●HCV●infection●and●related●liver●diseases.

Strain Name DPP4-HU

Cat. NO. NM-HU-190042

Background C57BL/6

Mutation Type Humanization

Strain Name CD81-HU

Cat. NO. NM-HU-190041

Background C57BL/6

Mutation Type Humanization

Strain Name OCLN-HU

Cat. NO. NM-HU-190072

Background C57BL/6

Mutation Type Humanization

Strain Name CD81&OCLN-HU

Cat. NO. NM-HU-2000107

Background C57BL/6

Mutation Type Humanization

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CD46-HUModel for meningococcal disease

●● Neisseria●meningitidis●is●a●major●cause●of●sepsis●and/or●meningitis.

●● These●bacteria●normally● cause●diseases●only● in●humans,●however,●mice●expressing●human●CD46●(hCD46)●are●susceptible●to●meningococcal●disease.

●● The●ROSA26●mouse●strain●has●one●copy●of●the●hCD46●inserted● into● chromosome● 6.● The● endogenous●ROSA26●promoter●drives●hCD46●expression●in●all●adult●tissues.

Strain Name R26-(SA-CD46-IRES-tdTomato)

Cat. NO. NM-KI-190087

Background C57BL/6

Mutation Type Knock-in

References for mouse models

1.● ●Ren●J,●Wang●L,●Chen●Z,●et●al.●Gene●expression●profile●of●transgenic●mouse●kidney●reveals●pathogenesis●of●hepatitis●B●virus●associated●nephropathy.●J●Med●Virol.●2006;78(5):551–560.

2.● ●Yan●H,●Zhong●G,●Xu●G,●He●W,●Jing●Z,●Gao●Z,●et●al.●Sodium●taurocholate●cotransporting●polypeptide●is●a●functional●receptor●for●human●hepatitis●B●and●D●virus.●eLife●2012;1●e00049.

3.● ●König●A,●Yang●J,●Jo●E,●et●al.●Efficient●long-term●amplification●of●hepatitis●B●virus●isolates●after●infection●of●slow●proliferating●HepG2-NTCP●cells.●J●Hepatol.●2019;71(2):289–300.

4.● ●Winer●BY;●Shirvani-Dastgerdi●E;●Bram●Y;●Sellau●J;●Low●BE;●et●al.●Preclinical●assessment●of●antiviral●combination●therapy●in●a●genetically●humanized●mouse●model●for●hepatitis●delta●virus●infection.●Sci●Transl●Med,●2018.●10(447).

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